Some treated patients completed an inpatient eating disorders program for the first time.

In a world first, a team of UHN scientists, led by TWRI Senior Scientist Dr. Andres Lozano, have shown that deep brain stimulation (DBS) in patients with anorexia helps to achieve and maintain improvements in body weight, mood and anxiety. DBS is a surgical procedure in which electrodes are implanted into specific parts of the brain to moderate the activity of dysfunctional areas. Anorexia is an eating disorder and psychiatric condition characterized by food restriction, body distortion and an overwhelming fear of gaining weight.

After a nine-month period following DBS surgery, the team observed that the patients had achieved weight gain—for these patients it was the longest period of weight gain since the onset of their illness. Patients also exhibited simultaneous changes in mood, anxiety, control over emotional responses, urges to binge and purge and other symptoms related to anorexia. “We are truly ushering in a new of era of understanding of the brain and the role it can play in certain neurological disorders,” says Dr. Lozano. “By pinpointing and correcting the precise circuits in the brain associated with the symptoms of some of these conditions, we are finding additional options to treat these illnesses.”

This work was supported by the Klarman Family Foundation and the Canadian Institutes of Health Research. A. Lozano is a Tier 1 Canada Research Chair in Neuroscience.

Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: a phase 1 pilot trial. Lipsman N, Woodside DB, Giacobbe P, Hamani C, Carter JC, Norwood SJ, Sutandar K, Staab R, Elias G, Lyman CH, Smith GS, Lozano AM. Lancet. 2013 March 6. [Pubmed abstract]

Medical imaging can detect hypoxic regions in tumours.

A lack of oxygen, known as hypoxia, is a common condition for cancer cells in solid tumours. Hypoxia in tumours is a major limiting factor in successful cancer treatment; hypoxic cells require nearly three times as much radiation to kill. OCI Senior Scientist Dr. Bradly Wouters and collaborators studied the mechanisms that confer hypoxia resistance to cancer cells and recently identified one signalling pathway that, when inhibited, could improve the response to treatment.

The hypoxia inducible factor pathway (HIF) and protein kinase r-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 α (eIF2α) both play a role in helping cancer cells survive the hypoxic environment of a tumour. Inhibiting either pathway decreased the fraction of surviving cells in hypoxic zones to a similar extent. HIF inhibition did not result in an improved response to radiation therapy, whereas blocking the PERK/eIF2α pathway led to “a striking improvement in tumour response to treatment,” according to Dr. Wouters. The study demonstrated that the PERK/eIF2α pathway mediates resistance to repeated cycles of hypoxia and oxygenation in tumours and that these cells were particularly important for the recovery and growth of tumours following radiation therapy.

This work was supported by the Dutch Science Organization, the Dutch Cancer Society, the Ontario Ministry of Health and Long-Term Care, The Terry Fox Research Institute, The Ontario Institute for Cancer Research, The Canadian Institutes of Health Research, The European Union Seventh Framework Programme/METOXIA and The Princess Margaret Cancer Foundation.

PERK/eIF2α signaling protects therapy resistant hypoxic cells through induction of glutathione synthesis and protection against ROS. Rouschop KM, Dubois LJ, Keulers TG, van den Beucken T, Lambin P, Bussink J, van der Kogel AJ, Koritzinsky M, Wouters BG. Proceedings of the National Academy of Sciences. 2013 March 19. [Pubmed abstract]

CR programs include exercise training, education and counselling.

Heart disease is the leading cause of death in women around the world. Cardiac rehabilitation (CR) is known to reduce death rates among these patients and improve their quality of life. Despite these benefits, women are less likely to be referred to CR than men. To better understand why this happens, a multi-centre study, led by TRI Adjunct Scientist and TGRI Scientist Dr. Sherry Grace, examined the different strategies used by Ontario hospitals to refer women to CR.

Cardiovascular disease patients completed a survey that assessed their CR referral and usage. Referral strategies used by hospitals included an automatic referral after discharge, a referral after a personal discussion with a health care provider, a combination of the two strategies or the current method of referral at the discretion of the health care provider. “We found that the combination of automatic and personal discussion-based referral strategies resulted in the greatest CR enrolment rates among women—10 times greater than the current method of referral,” says Dr. Grace. “Health care providers should be encouraged to discuss CR with all eligible women patients.”

This work was supported by the Canadian Institutes of Health Research and Heart and Stroke Foundation of Canada.

Effect of referral strategies on access to cardiac rehabilitation among women. Gravely S, Anand SS, Stewart DE, Grace SL; on behalf of the CRCARE Investigators. European Journal of Preventive Cardiology. 2013 March 11. [Pubmed abstract]